Assessing recovery after cold challenge and thumb involvement can help to rule out systemic sclerosis in patients presenting with Raynaud?s phenomenon

Objective: Our aim was to study whether recovery from a Raynaud?s attack and involvement of the thumb are differentiators for systemic sclerosis (SSc) in patients with Raynaud?s phenomenon (RP). Method: A stepwise cooling and recovery procedure was performed, provoking an RP attack, in patients with primary Raynaud?s phenomenon (PRP, n =?68) and SSc (n?=?18). During the procedure, the perfusion of all five fingers during cooling and recovery was assessed by photoelectric plethysmography. Results: In SSc patients, perfusion after 10?min in one or more fingers was more frequently not restored than in PRP patients (p?=?0.001), with a negative predictive value of 98%. The thumb was more frequently involved in SSc patients (p?=?0.036), with a negative predictive value of 95%. Positive predictive values were low. Conclusions: In patients with RP, when there is restoration of perfusion in all fingers after 10?min or when the thumb is spared, the presence of an underlying SSc is very unlikely. Although these results need to be validated in a clinical setting in a larger prospective study, these signs can help physicians to select additional testing for SSc in RP patients

Применение метода матричной прогонки для моделирования процесса пневматической обработки угольного пласта

Розглянуто чисельне рішення системи рівнянь математичної фізики, покладених в основу математичної моделі пневматичної дії на вугільний пласт, за допомогою методу матричної прогонки.The numerical solution of system of mathematical physics equations, formed the base of mathematical model of process of pneumatic action on coal stratum, using the method of matrix drive is considered

Polypharmacy and medication use in patients with chronic kidney disease with and without kidney replacement therapy compared to matched controls

BACKGROUND: This study aims to examine polypharmacy (PP) prevalence in patients with chronic kidney disease (CKD) Stage G4/G5 and patients with kidney replacement therapy (KRT) compared with matched controls from the general population. Furthermore, we examine risk factors for PP and describe the most commonly dispensed medications. METHODS: Dutch health claims data were used to identify three patient groups: CKD Stage G4/G5, dialysis and kidney transplant patients. Each patient was matched to two controls based on age, sex and socio-economic status (SES) score. We differentiated between ‘all medication use’ and ‘chronic medication use’. PP was defined at three levels: use of ≥5 medications (PP), ≥10 medications [excessive PP (EPP)] and ≥15 medications [hyper PP (HPP)]. RESULTS: The PP prevalence for all medication use was 87, 93 and 95% in CKD Stage G4/G5, dialysis and kidney transplant patients, respectively. For chronic medication use, this was 66, 70 and 75%, respectively. PP and comorbidity prevalence were higher in patients than in controls. EPP was 42 times more common in young CKD Stage G4/G5 patients (ages 20–44 years) than in controls, while this ratio was 3.8 in patients ≥75 years. Older age (64–75 and ≥75 years) was a risk factor for PP in CKD Stage G4/G5 and kidney transplant patients. Dialysis patients ≥75 years of age had a lower risk of PP compared with their younger counterparts. Additional risk factors in all patients were low SES, diabetes mellitus, vascular disease, hospitalization and an emergency room visit. The most commonly dispensed medications were proton pump inhibitors (PPIs) and statins. CONCLUSIONS: CKD Stage G4/G5 patients and patients on KRT have a high medication burden, far beyond that of individuals from the general population, as a result of their kidney disease and a large burden of comorbidities. A critical approach to medication prescription in general, and of specific medications like PPIs and statins (in the dialysis population), could be a first step towards more appropriate medication use

Chronic prescription of antidepressant medication in patients with chronic kidney disease with and without kidney replacement therapy compared with matched controls in the Dutch general population

BACKGROUND: Chronic kidney disease (CKD) is associated with a higher prevalence of depression, neuropathic pain and insomnia. These conditions are often treated pharmaceutically. In this study we aimed to determine the prevalence of chronic antidepressant use among CKD patients with and without kidney replacement therapy (KRT). METHODS: By using the Dutch health claims database, we were able to determine the prevalence, type and dosage of chronic antidepressant prescriptions in patients with CKD Stage G4/G5 without KRT (n = 14 905), patients on dialysis (n = 3872) and patients living on a functioning graft (n = 8796) and compared these to age-, sex- and socio-economic status (SES)-matched controls from the general population. RESULTS: Our data show that the prevalence of chronic antidepressant prescription is 5.6%, 5.3% and 4.2% in CKD Stage G4/G5, dialysis and kidney transplant patients, respectively, which is significantly higher than in matched controls. Although our data revealed more prescriptions in female patients and in the age category 45–64 years, our data did not show any association between antidepressant prescriptions and SES. Selective serotonin reuptake inhibitors were the most prescribed drugs in all patient groups and controls. Tricyclic antidepressants were more often used in patients compared with controls. CONCLUSION: This nationwide analysis revealed that chronic antidepressant prescription in the Netherlands is higher in CKD patients with and without KRT than in controls, higher in middle-aged patients and women, unrelated to socio-economic status and lower than chronic use reported in other countries

High-content high-throughput imaging reveals distinct connections between mitochondrial morphology and functionality for oxphos complex I, III, and V inhibitors

Cells can adjust their mitochondrial morphology by altering the balance between mitochondrial fission and fusion to adapt to stressful conditions. The connection between a chemical perturbation, changes in mitochondrial function, and altered mitochondrial morphology is not well understood. Here, we made use of high-throughput high-content confocal microscopy to assess the effects of distinct classes of oxidative phosphorylation (OXPHOS) complex inhibitors on mitochondrial parameters in a concentration and time resolved manner. Mitochondrial morphology phenotypes were clustered based on machine learning algorithms and mitochondrial integrity patterns were mapped. In parallel, changes in mitochondrial membrane potential (MMP), mitochondrial and cellular ATP levels, and viability were microscopically assessed. We found that inhibition of MMP, mitochondrial ATP production, and oxygen consumption rate (OCR) using sublethal concentrations of complex I and III inhibitors did not trigger mitochondrial fragmentation. Instead, complex V inhibitors that suppressed ATP and OCR but increased MMP provoked a more fragmented mitochondrial morphology. In agreement, complex V but not complex I or III inhibitors triggered proteolytic cleavage of the mitochondrial fusion protein, OPA1. The relation between increased MMP and fragmentation did not extend beyond OXPHOS complex inhibitors: increasing MMP by blocking the mPTP pore did not lead to OPA1 cleavage or mitochondrial fragmentation and the OXPHOS uncoupler FCCP was associated with OPA1 cleavage and MMP reduction. Altogether, our findings connect vital mitochondrial functions and phenotypes in a high-throughput high-content confocal microscopy approach that help understanding of chemical-induced toxicity caused by OXPHOS complex perturbing chemicals.Toxicolog

A risk profile for identifying community-dwelling elderly with a highrisk of recurrent falling: results of a 3-year prospective study

Introduction: The aim of the prospective study reported here was to develop a risk profile that can be used to identify community-dwelling elderly at a high risk of recurrent falling. Materials and methods: The study was designed as a 3-year prospective cohort study. A total of 1365 community-dwelling persons, aged 65 years and older, of the population-based Longitudinal Aging Study Amsterdam participated in the study. During an interview in 1995/1996, physical, cognitive, emotional and social aspects of functioning were assessed. A follow-up on the number of falls and fractures was conducted during a 3-year period using fall calendars that participants filled out weekly. Recurrent fallers were identified as those who fell at least twice within a 6-month period during the 3-year follow-up. Results: The incidence of recurrent falls at the 3-year follow-up point was 24.9% in women and 24.4% in men. Of the respondents, 5.5% reported a total of 87 fractures that resulted from a fall, including 20 hip fractures, 21 wrist fractures and seven humerus fractures. Recurrent fallers were more prone to have a fall-related fracture than those who were not defined as recurrent fallers (11.9% vs. 3.4%; OR: 3.8; 95% CI: 2.3-6.1). Backward logistic regression analysis identified the following predictors in the risk profile for recurrent falling: two or more previous falls, dizziness, functional limitations, weak grip strength, low body weight, fear of falling, the presence of dogs/cats in the household, a high educational level, drinking 18 or more alcoholic consumptions per week and two interaction terms (high educationx18 or more alcohol consumptions per week and two or more previous falls x fear of falling) (AUC=0.71). Discussion: At a cut-off point of 5 on the total risk score (range 0-30), the model predicted recurrent falling with a sensitivity of 59% and a specificity of 71%. At a cut-off point of 10, the sensitivity and specificity were 31% and 92%, respectively. A risk profile including nine predictors that can easily be assessed seems to be a useful tool for the identification of community-dwelling elderly with a high risk of recurrent falling. © International Osteoporosis Foundation and National Osteoporosis Foundation 2006